TITLE Gaba mod file only for fitting purpose
COMMENT
Thierry Nieus, unpublished results, please keep reserved.
Variables with suffix "_s" are meant for single IPSC fit, with suffix "_2" for CGP experimental condition
Does not work with variable dt!
ENDCOMMENT
NEURON {
POINT_PROCESS GRANULE_Gaba_stoch_vi
NONSPECIFIC_CURRENT i
RANGE Q10_diff,Q10_channel
RANGE g, ic ,Cdur ,Tmax, Erev
RANGE Open,Open_a6 :, ,OpenScaled,
:RANGE ScaleAlfa1,ScaleAlfa6,ScaleFactor_s
RANGE kon,koff,d3,r3,d1d2,r1r2,a1,b1,a2,b2,r1,r2,d1,d2
RANGE kon_a6,koff_a6,d3_a6,r3_a6,d1d2_a6,r1r2_a6,a1_a6,b1_a6,a2_a6,b2_a6,r1_a6,r2_a6,d1_a6,d2_a6
RANGE gmaxA1,gmaxA6,onSET
RANGE gA1,gA6
RANGE xout,yout,zout,uout
:RANGE tau_1,tau_rec,tau_facil, U
RANGE T,U_2
RANGE diff_flag,diff_flag2,M,Rd,Diff,lamd
RANGE nd,diffus ,Trelease, gmax_factor, syntype
}
UNITS {
(nA) = (nanoamp)
(mV) = (millivolt)
(umho) = (micromho)
(mM) = (milli/liter)
(pS) = (picosiemens)
PI = (pi)(1)
}
PARAMETER {
syntype
gmax_factor = 1
: Parametri Postsinaptici
gmaxA1 = 918.807 (pS)
gmaxA6 = 132.842 (pS)
Q10_diff = 1.5
Q10_channel = 2.4
Cdur = 0.3 (ms)
Cdur_2 = 0.3 (ms)
: A1 kinetic rates EC50=(around) 20 uM, U=0.35
kon = 17.7 (/ms/mM) : 20
koff = 2 (/ms)
d3 = 21.703 (/ms) : 15
r3 = 0.97325 (/ms) : 0.15, use 3.75 for slices in the PR model
d1d2 = 0 (/ms/mM) : 15
r1r2 = 0 (/ms) : 0.007
a1 = 0.4144 (/ms) : 0.06
b1 = 0.03 (/ms)
a2 = 1.0002 (/ms) : 0.4
b2 = 10 (/ms)
r1 = 7e-4 (/ms)
r2 = 0.14208 (/ms) : 6e-3
d1 = 3.3e-4 (/ms)
d2 = 3.4898 (/ms) : 1.2
: A6 kinetic rates according bifit_gaba_ver5.conf have EC50 curve max value 0.727 with pulse 400ms, EC50=1.5uM
kon_a6 = 54.8 (/ms/mM) :20
koff_a6 = 0.31061 (/ms) :2
d3_a6 = 15 (/ms)
r3_a6 = 7.4132 (/ms) :3.75
d1d2_a6 = 24.2 (/ms/mM) :15
r1r2_a6 = 0.091668 (/ms) :0.007
a1_a6 = 0.06 (/ms)
b1_a6 = 0.03 (/ms)
a2_a6 = 0.4 (/ms)
b2_a6 = 10 (/ms)
r1_a6 = 0.040001 (/ms) :7e-4
r2_a6 = 0.4316 (/ms) :6e-3
d1_a6 = 0.86042 (/ms) :3.3e-4
d2_a6 = 2.7012 (/ms) :1.2
Erev = -65 (mV)
: Parametri Presinaptici
:tau_1 = 0.1 (ms) < 1e-9, 1e9 >
:tau_rec = 36.169 (ms) < 1e-9, 1e9 > :43.4
:tau_facil = 58.517 (ms) < 0, 1e9 > : 6.22
:U = 0.35 < 0, 1 >
T_factor = 0.5
Tmax = 1 (mM)
onSET = 1
: Diffusion parameters
: Diffusion: M=21.500, R=1.033, D=0.223, lamd=0.02 as in excitatory synapses
M = 7.506 : numero di (kilo) molecole in una vescicola (52.76)
Rd = 0.978 (um) :4.79 :4.96 : 4.96 (first fit!)
Diff = 0.223 (um2/ms)
lamd = 20 (nm)
diff_flag = 1 : flag diffusion on/off
nd = 1 : kernel exponent of diffusion
celsius (degC)
}
ASSIGNED {
v (mV) : postsynaptic voltage
i (nA) : current = g*(v - Erev)
ic (nA) : current = g*(v - Erev)
g (pS) : conductance
gA1 (nA)
gA6 (nA)
Open
Open_a6
diffus
T (mM)
Trelease (mM)
Mres (mM)
tpre (ms)
xout
yout
zout
uout
tspike[100] (ms) : will be initialized by the pointprocess
PRE[100]
:PRE_2[500]
numpulses
tzero
gbar_Q10 (mho/cm2)
Q10 (1)
}
STATE {
: CTRL - A1
C
CA1
CA2
DA1
DA2
DA2f
OA1
OA2
: CTRL - A6
C_a6
CA1_a6
CA2_a6
DA1_a6
DA2_a6
DA2f_a6
OA1_a6
OA2_a6
}
INITIAL {
: CTRL - A1
C=1
CA1=0
CA2=0
DA1=0
DA2=0
DA2f=0
OA1=0
OA2=0
CA1=0
CA2=0
: CTRL - A6
C_a6=1
CA1_a6=0
CA2_a6=0
DA1_a6=0
DA2_a6=0
DA2f_a6=0
OA1_a6=0
OA2_a6=0
CA1_a6=0
CA2_a6=0
Open=0
T=0 (mM)
gbar_Q10 = Q10_diff^((celsius-30)/10)
Q10 = Q10_channel^((celsius-30)/10)
numpulses=0
Mres=1e3* (1e3 * 1e15 / 6.022e23 * M) : (M) to (mM) so 1e3, 1um^3=1dm^3*1e-15 so 1e15
FROM i=1 TO 100 { PRE[i-1]=0 tspike[i-1]=0 } :PRE_2[500]=0}
tspike[0]=1e12 (ms)
:if(tau_1>=tau_rec){
: printf("Warning: tau_1 (%g) should never be higher neither equal to tau_rec (%g)!\n",tau_1,tau_rec)
: tau_rec=tau_1+1e-5
: :printf("tau_rec has been set to %g\n",tau_rec)
:}
onSET = 1
}
FUNCTION imax(a,b) {
if (a>b) { imax=a }
else { imax=b }
}
FUNCTION diffusione(){
LOCAL DifWave,i,cntc,fi
DifWave=0
cntc=imax(numpulses-100,0) : ??????
FROM i=cntc TO numpulses{
fi=fmod(i,100)
tzero=tspike[fi]
if(t>tzero){
DifWave=DifWave+PRE[fi]*Mres*exp(-Rd*Rd/(4*Diff*(t-tzero)))/((4*PI*Diff*(1e-3)*lamd)*(t-tzero))^nd
}
}
diffusione=DifWave
}
BREAKPOINT {
SOLVE kstates METHOD sparse
Open=OA1+OA2
Open_a6=OA1_a6+OA2_a6
gA1 = gmaxA1 * gbar_Q10 * Open
gA6 = gmaxA6 * gbar_Q10 * Open_a6
g = (gA1 + gA6) * gmax_factor
i = (1e-6) * g * ( v - Erev )
ic = i
}
KINETIC kstates {
: ************
: *** CTRL ***
: ************
diffus=diffusione()
Trelease = T + diffus
: *** ALFA 1 ***
: second row
~ C <-> CA1 (2*kon*Trelease*Q10,koff*Q10)
~ CA1 <-> CA2 (kon*Trelease*Q10,2*koff*Q10)
~ CA2 <-> DA2f (d3*Q10,r3*Q10)
: third row
~ DA1 <-> DA2 (d1d2*Trelease*Q10,r1r2*Q10)
: first <=> second row
~ OA1 <-> CA1 (a1*Q10,b1*Q10)
~ OA2 <-> CA2 (a2*Q10,b2*Q10)
: third <=> second row
~ DA1 <-> CA1 (r1*Q10,d1*Q10)
~ DA2 <-> CA2 (r2*Q10,d2*Q10)
CONSERVE C+CA1+CA2+DA1+DA2+DA2f+OA1+OA2=1
: *** ALFA 6 ***
: second row
~ C_a6 <-> CA1_a6 (2*kon_a6*diffus*Q10,koff_a6*Q10)
~ CA1_a6 <-> CA2_a6 (kon_a6*diffus*Q10,2*koff_a6*Q10)
~ CA2_a6 <-> DA2f_a6 (d3_a6*Q10,r3_a6*Q10)
: third row
~ DA1_a6 <-> DA2_a6 (d1d2_a6*diffus*Q10,r1r2_a6*Q10)
: first <=> second row
~ OA1_a6 <-> CA1_a6 (a1_a6*Q10,b1_a6*Q10)
~ OA2_a6 <-> CA2_a6 (a2_a6*Q10,b2_a6*Q10)
: third <=> second row
~ DA1_a6 <-> CA1_a6 (r1_a6*Q10,d1_a6*Q10)
~ DA2_a6 <-> CA2_a6 (r2_a6*Q10,d2_a6*Q10)
CONSERVE C_a6+CA1_a6+CA2_a6+DA1_a6+DA2_a6+DA2f_a6+OA1_a6+OA2_a6=1
}
NET_RECEIVE(weight,on, nspike,tzero (ms),x,y,z,u, tsyn (ms)) {LOCAL fi
INITIAL {
:x = 0
:y = 0
:z = 0
:u = 0
:xout=x
:yout=y
:zout=z
:uout=u
:tsyn = t
nspike = 1
}
if(onSET){
on=0
onSET=0
}
if (flag == 0) {
: Qui faccio rientrare la modulazione presinaptica
nspike = nspike + 1
:printf("T = %g (mM)\n",Trelease)
if (!on) {
tzero = t
tpre=t : activates diffusion
on = 1
:z = z*exp(-(t - tsyn)/tau_rec)
:z = z + ( y*(exp(-(t - tsyn)/tau_1) - exp(-(t - tsyn)/tau_rec)) / ((tau_1/tau_rec)-1) )
:y = y*exp(-(t - tsyn)/tau_1)
:x = 1-y-z
:if (tau_facil > 0) {
: u = u*exp(-(t - tsyn)/tau_facil)
: u = u + U * ( 1 - u )
:} else { u = U }
:y = y + x * u
T=Tmax*T_factor :*y
fi=fmod(numpulses,100)
PRE[fi]=T_factor :y : PRE[numpulses]=y
tspike[fi] = t
numpulses=numpulses+1
:tsyn = t
}
net_send(Cdur, nspike)
}
if (flag == nspike) {
T = 0
on = 0
}
}